The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis

BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.     

Performance status and comorbidity predict transplant-related mortality after allogeneic hematopoietic cell transplantation.

Comorbidity measurements have recently been used to improve estimation of tolerance to allogeneic hematopoietic cell transplantation (HCT). We sought to determine the independent effect of comorbidity and performance status on HCT outcome and to devise a simple risk classification system for transplant-related mortality. We analyzed 105 consecutively enrolled patients who underwent HCT and received reduced intensity conditioning with fludarabine, melphalan, and alemtuzumab. Comorbid conditions were tabulated using 2 scales, the Charlson Comorbidity Index (CCI) and the Kaplan-Feinstein Scale (KFS). Comorbid conditions were found in 47% of patients by the KFS and in 27% by the CCI (P < .001). Using the Eastern Cooperative Oncology Group Performance Status (PS) scale, 34% had a PS score >0 (range, 0-2). A simple scale combining the KFS and PS enabled separation of high- from low-risk patients, with 6-month cumulative incidences 50% and 15%, respectively for transplant-related mortality (P = .001) and enhanced prognostic power over the CCI alone (P = .018). Prospective studies evaluating more comprehensive functional and comorbidity measurements are warranted.     

Intraparenchymal pulmonary lymph node: case report and literature review

Summary A case of a 44-year-old woman with a solitary pulmonary coin lesion is presented. Histologic study of this nodule revealed a normal intraparenchymal pulmonary lymph node. A review of the literature discusses the incidence and characteristics of this entity.

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Nud lymphatique intrapulmonaire: revue de la littérature. A propos d'un cas

Résumé L'observation d'un cas de lésion nodulaire du poumon est rapportée chez une femme de 44 ans. L'étude histologique du nodule a révélé un nud lymphatique intrapulmonaire normal. La revue de la littérature apprécie l'incidence et les caractéristiques de cette localisation.

     

The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Outcome Following Electroconvulsive Therapy: A Comparison of Primary and Secondary Depression

In a consecutive series of 117 depressed patients referred for electroconvulsive therapy, the 10 with secondary depression had significantly poorer outcomes according to three independently assessed measures-Hamilton rating scale score at discharge, global rating at discharge, and mean depressive symptom score during a 6-month follow-up.     

Master indenture: capital financing for health care systems

The master indenture enables members of multiinstitutional health care systems to finance capital programs and expansions by borrowing on the basis of systemwide revenues and assets. Participation in a master indenture financing may be structured in two ways. In a restricted group, only the parent organization issues notes, and only the parent is directly liable for the debt. To ensure that each member's revenues flow to the parent, the latter must have sole member status and be permitted to approve subsidiaries' debts, budgets, amendments to articles and bylaws of incorporation, and selection of trustees. Each entity's articles and bylaws must permit it to support the system members' common charitable purpose. In contrast, members of an obligated group have direct joint and several liability for master indenture notes. If one subsidiary misses a payment, the parent can call for payment from other obligated group members. Limitations on a member's obligation to support system debt in case of insolvency or bankruptcy may be included in the master indenture provisions. Whichever structure is selected, the amount of debt that can be incurred is based on the institutions' combined financial statements. The master indenture thus allows financially weak institutions to benefit from the credit strengths of stranger system members and permits the parent organization to control members' access to capital markets.     

Nurse Decision-making for Suspected Urinary Tract Infections in Nursing Homes: Potential Targets to Reduce Antibiotic Overuse

ObjectivesTo determine what information is most important to registered nurses' (RNs) decisions to call clinicians about suspected urinary tract infections (UTIs) in nursing home residents.DesignWeb-based discrete choice experiment with 19 clinical scenarios.Setting and ParticipantsOnline survey with a convenience sample of RNs (N = 881) recruited from a health care research panel.MethodsClinical scenarios used information from 10 categories of resident characteristics: UTI risk, resident type, functional status, mental status, lower urinary tract status, body temperature, physical examination, urinalysis, antibiotic request, and goals of care. Participants were randomized into 2 deliberation conditions (self-paced, n = 437 and forced deliberation, n = 444). The degree to which evidence- and non–evidence-based information was important to decision-making was estimated using unconditional multinomial logistic regression.ResultsFor all nurses (22.8%) and the self-paced group (24.1%), lower urinary tract status had the highest importance scores for the decision to call a clinician about a suspected UTI. For the forced-deliberation group, body temperature was most important (23.7%), and lower urinary tract status was less important (21%, P = .001). The information associated with the highest odds of an RN calling about a suspected UTI was painful or difficult urination [odds ratio (OR) 4.85, 95% confidence interval (CI) 4.16–5.65], obvious blood in urine (OR 4.66, 95% CI 3.99–5.44), and temperature at 101.5° (OR 3.80, 95% CI 3.28–4.42). For the self-paced group, painful or difficult urination (OR 5.65, 95% CI 4.53–7.04) had the highest odds, whereas obvious blood in urine (OR 4.39, 95% CI 3.53–5.47) had highest odds for the forced-deliberation group.Conclusions and ImplicationsThis study highlighted the importance of specific resident characteristics in nurse decision-making about suspected UTIs. Future antimicrobial stewardship efforts should aim to not only improve the previously studied overprescribing practices of clinicians, but to improve nurses' assessment of signs and symptoms of potential infections and how they weigh resident information.